The proposed studies will investigate interactions between cortical and subcortical brain regions during speech production by measuring regional cerebral blood flow (rCBF) with positron emission tomography (PET) in Parkinson's disease (PD) subjects, PD subjects with deep brain stimulation (DBS) of the subthalamic nuclei (STN), and normal subjects. The use of DBS of the STN to treat PD provides a reversible means of modifying the activity of sub-cortical areas including the striatum, globus pallidus, and thalamus. While effective in reducing non-speech motor symptoms, this form of therapy often has no effect or even a negative effect on speech, raising questions about the relationship between speech and non- speech motor control in PD, and more generally, about the nature of cortical-subcortical interactions during speech. We have previously observed a reliable inverse relationship between rCBF in the caudate and inferior frontal area as a function of speech rate in normal and ataxic speakers. The proposed studies will further explore this relationship and the ways in which it is altered by PD and by DBS of the STN by mapping brain activity during a series of controlled speech production tasks. The concurrent measurement and subsequent analysis of rCBF and speech production has already produced significant insight into the functional significance of imaging data. The proposed studies should yield significant progress in understanding cortical-subcortical interactions during speech in normal speakers and in speakers whose fluency has been affected by PD and DBS. This project will also characterize how such interactions are affected by task demands, and how PD, DBS, and task demands interact. The goal is to better understand cortical-subcortical interactions in normal and dysfluent speech, and the role of-such interactions in specific aspects of speech production. The ability to speak clearly involves a complex brain system that is not fully understood. Parkinson's disease interferes with this ability. This research will study the effects of Parkinson's disease and one form of treatment on brain activity during speech to better understand this system. This may lead to new therapies for speech disorders in neurological diseases. [unreadable] [unreadable] [unreadable]